Project summary

The Consortium aspBIOmics aims to identify and to characterize new biomarkers for an effective management of invasive aspergillose (IA). Thereby, aspBIOmics focuses on a new, complementary approach; we will analyze the relevance of pathogen- as well as host- (patient-) parameters. Such an extensive additional knowledge on IA will allow a more successful outcome of this devastating disease.

The data generated within aspBIOmics will allow systematic analyses of the complete pathophysiology of IA, including diagnosis, resistance to antifungals, as well as genetic susceptibility to IA. In addition, we will develop commercial assays for an improved diagnosis of IA.

The consortium aspBIOmics consists of 5 different Work packages (WP). WP1 bases on the analysis of biomarkers of A. fumigatus (RNA, DNA, proteom analyses in clinical specimens), while WP2 focusses on the analysis of markers related to the immune response of patients (multiplex-ELISA assays, transcriptome analyses of immune cells ex vivo). In WP4, we will perform genetic-epidemiological analyses of risk markers of IA (arrays, functional analyses). In WP 5, we have included the sample archive, the data archive, the data management, as well as the development of commercial assays.

Global interaction of A. fumigatus with the human immune system

Meetings

The initial meeting of aspBIOmics was held on 31 May 2011 in Frankfurt, Germany. All partners of the consortium were present at this meeting. The partners agreed to initiate all 5 Work Packages.s host- (patient-) parameters. Such an extensive additional knowledge on IA will allow a more successful outcome of this devastating disease.

Participants of the inital meeting in Frankfurt

Goals

During the aspBIOmics project, we aim to reach the following milestones:

Development of a sensitive and specific nucleic acid based detection method

Development of a sensitive and specific antigen based detection method

Discriminative role of antigens / antibodies during IA infection

Identification of cytokines and chemokines correlated with development of IA

Responses of the innate immune cells to causes of IA infection

Development of methods for the detection of relevant biomarkers of IA

Molecular understanding of the resistance to antifungals used to treat IA

Fitness of resistant strains in vivo

Development of a method to survey resistant strains

Definition of SNP associated to IA

Functional relevance of selected SNP

Association of SNP, which are genetically and functionally relevant to IA

Collection and maintenance of clinical specimens from haematological patients

Collection of host, clinical and mycology data from all patients according to the EORTC / MSG diagnostic criteria

Global development of new diagnostic methods for IA

Invasive aspergillosis

Invasive aspergillosis (IA) is the most common cause of infection-associated mortality in patients being treated for haematological malignancies and is an emerging disease in solid organ transplant recipients, critical care patients and in those receiving novel immunomodulatory therapies. Although, IA may be perceived to be an uncommon disease, with an incidence of 10,000 patients annually in Europe, there is increasing evidence that this infection is affecting a broader range of patient groups (Lerventakos et al., 2010, Clin Infect Dis 50: 405).

Aspergillus fumigatus is the most commonly isolated species from cases of IA and is the focus of our research, although we believe the intended outcomes will act as a paradigm for management of IA due to less common species such as A. flavus and the emerging A. terreus.

Pulmonary involvement was present in 97% of patients with Aspergillus infections, and the infection was widely disseminated to various organs in 25% of patients. The incidence in stem cell transplant patients has ranged from 5 - 20%, with a higher frequency in patients suffering from graft-versus-host disease (GVHD); mortality rates are 68 to 100% (Marr, 2010, Curr Opin Oncol 22: 138).

Deutsche Forschungsgemeinschaft, Schwerpunktprogramm 1160, „Analysis of the interaction between Aspergillus fumigatus and human immune effector cells and the induction of innate and adaptive immune responses to this pathogen”